ES2371337T3 - METHOD TO TREAT AN IMPLANT, AND SUCH IMPLANT. - Google Patents

Abstract

The invention relates to a method for treating an implant, and to an implant treated by said method. All or some of the outer surfaces of the implant are oxidized with a layer (1a) of substantial thickness and substantial porosity or pore volume. One or more CaP layers (12) are applied to the porous surface or surface of large pore volume. Bone-growth-stimulating agents (13), for example rh-BMP-2 or rh-BMP-7, are then applied to the CaP layer. The method and the device make it possible to support a maximum quantity of bone-growth-stimulating agent, which can be controlled in respect of its release function.

Description

Method for treating an implant, and said implant

The present invention relates to a method for further treating an implant that has been manufactured from a histocompatible material, preferably titanium, and is produced from an initial piece of said material. The invention also relates to an implant made of this histocompatible material.

The use of coatings that stimulate bone growth of CaP (calcium phosphate compounds), for example in the form of HA (hydroxyapatite), is also known in relation to implants. These can be applied, for example, by a sputtering method, in the form of the so-called RF sputtering with subsequent heat treatment. In this sense, it is known how to use the CaP layer as a base or reservoir for agents or substances that stimulate bone growth, which include growth and differentiation factors. Such agents or substances that stimulate bone growth comprise growth and differentiation factors and may include, for example, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor (TGF). ) or substances belonging to the TGF-� superfamily, such as BMP (bone morphogenetic proteins). In this regard, reference is made, among others, to WO-A-00 72 775, submitted by the same applicant, and to the relevant prior art fields cited therein.

WO-A-00 72 775 discloses a dental implant, preferably made of titanium, which is coated with a calcium phosphate compound with a thickness between a few Angströms and 20 µm. The layer of calcium phosphate compound can have a degree of crystallization between 75% and 100% or between 0% and 75%. A layer of agent that stimulates bone growth, such as BMP, is applied to this layer of calcium phosphate compound. The layer of agent that stimulates bone growth has a thickness between a few Angströms and 1 µm.

WO-A-00 72 776 discloses a dental implant, preferably made of titanium, which is oxidized to provide an oxide layer between 0.5 µm and 10 µm thick. The oxide layer has a surface roughness within the range of 0.4 µm and 5 µm. A layer of agent that stimulates bone growth, such as TGF-�, is applied to this oxide layer.

WO-A-00 72 777 discloses a dental implant, made of titanium, which is oxidized to provide an oxide layer of a thickness between 1 µm and 20 µm. The oxide layer has a surface roughness within the range of 1 µm and 5 µm and is highly porous, with pore diameters in the range of 0.01 µm and 10 µm. A layer of agent that stimulates bone growth, such as BMP, is applied to this oxide layer.

WO-A-02 78 759, published on 10.10.2002, discloses a dental implant made of titanium, covered by an oxide layer, which is further covered by a layer of a calcium phosphate compound of a thickness between 0.1 µm and 50 µm.

In relation to implants in dental contexts, for example in the jaw bone, there is a need to achieve a high degree of treatment individuality due to the presence of structures, physical responses, acidity levels, etc. of said bone widely variable. Therefore, there is a need to be able to achieve the desired implant properties in different people who can react very differently to coatings or substances that stimulate bone growth. By choosing the porosity and the thickness of the oxide layer of the material, for example the titanium oxide layer, the implant material can stimulate, by itself, the incorporation process, and the use of coatings / agents that Stimulate bone growth can be combined with the choice of porosity and the thickness of the oxide layer to allow further stimulation. The invention aims to solve this problem, among others, and proposes implant structures that adapt to different treatment situations.

It is useful to use coatings and agents and methods that are known per se, so that the desired results are not ambiguous. The invention also aims to solve this problem.

In certain treatment situations, there is therefore a need to be able to supply and control relatively large amounts of agents or substances that stimulate bone growth and maintain bone growth. The invention proposes, for example, primary and secondary deposits for said coatings or substances. In this context, a problem is to combine the structure of the oxide layers with the layers of CaP / HA and the agent that stimulates bone growth in such a way that the most effective results are achieved in different individual cases. The invention also solves this problem.

What can be considered mainly as a characterizer of the method is the use of three successive treatment stages. In the first stage of treatment, all or some of the outer surfaces of the implant are oxidized with a layer of substantial thickness, meaning in this case a thickness of more than 5 µm, and with a porosity or a substantial pore volume. In the second stage, a compound or compounds of calcium phosphate (CaP), preferably in the form of hydroxyapatite (HA), are applied to the porous surface or surfaces. In the third stage, an agent / substance that stimulates bone growth is applied to the layer, preferably after the application of CaP has been completed. The invention is defined in claims 1 and 2.

In further developments of the new method, one or several first implant surfaces are provided with said oxide layer that is coated with calcium phosphate compound or compounds or with said coatings or agents that stimulate bone growth. One or more second surfaces on the oxide layer are coated with agents that stimulate bone growth or with said calcium phosphate compound or compounds, such that the first and second surfaces have oxide layers of said type, but the oxide layer

10 is coated differently, that is, with coating or coatings or agents that stimulate bone growth, in one case, and calcium phosphate compound or compounds, in the other.

All or part of the exterior of the implant may be provided with an oxide layer of substantial thickness and with a pore arrangement that in one embodiment may have a porosity or a substantial pore volume. The

The pore arrangement is designed, in this case, to receive one or several first layers of CaP coatings. The second layers of agents / substances that stimulate bone growth are arranged on the arrangement of pores, in the upper part of said layers of CaP / HA.

In further developments of the invention, the intermediate layer or layers of CaP / HA have a double function, in the

20 that, in a first function, the layer in question, together with the thick porous layer of oxide, forms a storage or storage base for the layer of agent that stimulates bone growth, which is on the outside. In addition, the CaP / HA layer participates in the function that stimulates bone growth or the function that maintains bone growth, preferably working the CaP layer or layers with a greater temporal perspective for their release, compared to the agent layers that Stimulates bone growth.

In further developments of the inventive concept, the implant has first and second surfaces provided with oxide layers, but each one is provided with CaP / HA or agent that stimulates bone growth, such that different structures or coatings of layers are present on the first and second surfaces. In a preferred embodiment, the CaP coating may have a thickness within the range of a few

30 Angströms at 20 µm. The layer of agent that stimulates bone growth preferably has a thickness between a few Angströms and 1 µm. The CaP has a chosen degree of crystallization. The CaP layer can be applied by sputtering (for example, sputtering with magnetron) of a substantially amorphous CaP substance at first and subsequent heat treatment. When the implant material is for example titanium, the application and heat treatment of the CaP is such that subsidence is achieved in the layer of

35 CaP, which can contribute to the anchoring of the layer of agent that stimulates bone growth.

In addition, the implant can have surfaces without a layer of porous oxidation and coated with CaP and agent that stimulates bone growth or with CaP or only agent that stimulates bone growth.

Additional features of the invention will be apparent from the appended claims of the patent. Through what has been proposed above, it is possible to satisfy treatment situations in which there is a need for a maximum amount of agents or substances that stimulate bone growth that are intended to be supported by the implant. The structure of the oxide layer itself has properties that favor bone growth and bone incorporation and that can now be complemented with coatings,

45 substances and agents of said type. The temporary appearance of the release of coatings, agents or substances in the implanted state can be set within wide limits. According to the invention, different parts of the implant can be provided with different combinations of layers of oxide, CaP and bone growth stimulating agent, which can provide the desired consolidation and growth effects at different levels or circumferences of the jaw implant / bone . Proven and verified techniques can be used.

The embodiments proposed in the present application of a method and an implant according to the invention will be described below with reference to the attached drawings, in which:

Figure 1 shows, on a very enlarged scale, a vertical section through the implant and a part of the oxide layer 55 disposed thereon and interacting with a bone, for example a jaw bone,

Figure 2 shows, in the form of a block diagram, the production of an implant from an initial piece, 60 Figures 3 to 6 show different stages of treatment of the implant produced according to Figure 2, and

Figure 7 shows, schematically in a vertical view, an implant that has been treated in said stages according to Figures 3 to 6. 65

65 E02744042 08-11-2011

In Figure 1, reference numeral -1-indicates an implant, or rather parts of an implant. The implant is arranged in a manner known per se in bone -2- (partially shown) of the jaw. The implant has an non-oxidized part -1a- and an oxide layer -1b-. The oxide layer has a substantial thickness -T-. The oxide layer is provided with a pore arrangement in which, in Figure 1, several pores -2-, -3-, -4- and -5- have been shown. The pores bifurcate inwards from the outside -1b'- of the surface layer into the layer -1b ”that joins in said solid part -1a-. In the present case, there are pore channels that narrow inwards from the outside, in the direction of the inner parts -1b "- of the oxide layer. Said pore narrowing parts have been indicated by -6-, -7-, -8-, -9-, -10-, -11-. According to the inventive concept, the appearance of the pores and the channels in the layer can be varied considerably depending on the production method and the parameters of the production of the oxide layer. According to an idea of the invention, the pore arrangement will first be provided with one or several layers of CaP calcium phosphate compounds. In Figure 1 it has been indicated by -12-said coating of CaP. Depending on the method of application for the CaP layer, the layer or layers may be provided with different thicknesses, as can be seen from the figure. Thus, -2a- and -2b- indicate that thicker CaP layers are present on parts of the CaP layer development. One or several layers of substance -13- that stimulates bone growth have been applied on the outside of said CaP layers. Depending on the development of the oxide layer on its exterior, the layer 13 may adopt different thicknesses. In the present case, an example has been shown in which the layer of agent that stimulates bone growth is thicker than the layer or layers of CaP. In other illustrative embodiments, the position of the thicknesses can be reversed.

The substance 13 that stimulates bone growth may be one of the agents or substances that stimulate bone growth mentioned in the introduction, for example BMP, preferably rhBMP-2 and / or rhBMP-7.

Figure 1 also indicates that body substances or substances are released from the jaw bone for a certain time after the implant has been implanted in the jaw bone. This has been shown by the arrows -14-directed towards the implant. According to the invention, the substances or agents between

or on the implant will be released in the opposite direction. The release of body substances and the release of the implant coatings have been indicated by the arrows -15-. Once a certain degree of release of the outer layer of agent that stimulates bone growth has occurred, the release of the layer or layers of CaP begins, which has been indicated by the dashed arrows -16-. The substances enter the space or interstitium between the jaw bone and the implant, whose interstitium will be filled by bone growth in bone -2- of the jaw. Said bone growth also causes the jaw bone to grow into the pore system and, after the release of both the agent layer that stimulates bone growth and the CaP layer, bone growth collaborates with the system of pores and titanium oxide in the latter, which, in accordance with the above, also stimulates bone growth.

In the block diagram in Figure 2, reference numeral -18- indicates a production apparatus or a production station for implants. Production involves the work of initial pieces of histocompatible material, preferably in the form of titanium -19-. One of said initial pieces has been indicated by -19-. An implant -20- is collected from the station -18- and is further treated in the functional stages according to Figures 3, 4, 5 and 6.

In Figure 3, the oxide layer is produced on all or part of the implant -20- by anodic oxidation, which is an electrochemical method. The relevant surfaces of the implant are exposed so that, after immersion in a container -21- containing electrolyte -22-, oxidation of the surfaces in question takes place. The method is known per se and, therefore, will not be described in this document. However, it will be noted that the method uses a voltage source -23- and a cathode -24-. Before treatment at the station according to figure 3, the implant has been mechanically worked by turning, milling, polishing, etching, etc. The parts of the implant that are not to be provided with oxide layers are protected in a manner known per se. The structure of the oxide layer can be affected by several parameters in the process, for example the composition and temperature of the electrolyte, the applied voltage and current, the geometric shape of the electrode, the treatment time, etc. The station, as such, is indicated by -24- in Figure 3. After preparation at the station -24-, the implant -20- is transferred to the station -25- according to Figure 4. The outer parts - 20a- or the relevant surface parts of the implant will be provided in whole or in part with a coating or coatings similar to a film or a layer. This can be done in a manner known per se in a chamber -26-, and the coating can be applied by means of the so-called "sputtering with RF" or "sputtering with magnetron". In this regard, reference may be made, among others, to PCT application number WO 98/48862. In the chamber, one or more calcium phosphate compounds -27- are applied or sprayed cathodically on the surface or parts of the implant surface. The implant -20- is then transferred to an oven -28-, in which said implant is subjected to a heat treatment. You can choose temperatures, for example 600oC, and times for the treatment in saturated steam. The heat treatment provides partial crystallization of the coating applied in the chamber -26-. In the present case, an adequate degree of crystallization is between 25 and 75%, which will be set in relation to the degree of crystallization of 0% applicable to the radiologically amorphous surface in which the particle size is around 50 nm. The degree of crystallization can be, for example, from 25 to 75% or from 75 to 100%. In the case of three layers or coatings, for example, the degree of crystallization in layer -1- can be 75 to 100%, and in layer -2- it can be 25 to 100%, while layer - 3- is amorphous.

After treatment in the oven -29-, the implant -20- is transferred to the station, according to figure 6, for application of the agent that stimulates bone growth, in accordance with the above. According to Figure 6, a container -30- is used in which an agent solution that stimulates bone growth is indicated by -31-. The

The immersion takes place during a chosen time that is adjusted with respect to the release function of the agent layer that stimulates bone growth (wet chemical deposition) on the implant, at the time of drying and / or another parameter.

Figure 7 shows the fully treated implant. The implant can comprise, for example, three surfaces

10 different -32-, -33-, -34-, all surfaces of the described oxide layer being provided, with a first surface -32- only of CaP, a second surface -33- only of agent that stimulates the bone growth, and the surface -34- of both CaP and agent that stimulates bone growth, according to the figure

one.

The CaP coating may have a thickness within the range of a few Angströms at 20 µm, while the layer of agent that stimulates bone growth may be between a few Angströms and 1 µm thick. These values must be considered as average values (see layer 13 in Figure 1). The oxide layer may have a surface roughness in the range of 0.4 to 5 µm. The oxide layer is highly porous, with a number of pores from 1 x 107 to 1 x 1010 pores / cm2. Each surface of the oxide layer has mainly pores with

20 diameter sizes within the range of 0.1 to 10 µm and / or a total pore volume that is in a range of 5 x 10-2 and 10-5 cm3. The inner layers can have a higher degree of crystallization than the outer layers, and the innermost CaP layer can thus have a degree of crystallization of 75 to 100%.

Claims (9)

1. Method for further treating an implant (20) of histocompatible material, preferably titanium, and produced from an initial piece (19) of said material, in which all or some of the outer surfaces 5 of the implant (20) are oxidized to provide an oxide layer (1b) of substantial thickness, preferably with a thickness of more than 5 µm, and with substantial porosity or pore volume, characterized in that

-

 a calcium phosphate compound (12), preferably in the form of hydroxyapatite, is applied to the porous surface

of the oxide layer (1b), and because 10

-

 An agent (13) that stimulates bone growth is then applied on top of the calcium phosphate compound (12), preferably after the latter has been completely dried.

2. Implant (20) made of histocompatible material, preferably titanium, in which all or part of the 15 outer surfaces (34) of the implant (20) are provided with an oxide layer (1b) of substantial thickness and a pore arrangement having a porosity or a substantial pore volume, characterized by one or more layers of compound of calcium phosphate (12) arranged on the pore arrangement of the oxide layer (1b), and by a layer of an agent (13) that stimulates bone growth, preferably BMP, for example rhBMP-2

or rhBMP-7, disposed on top of said layer or layers of calcium phosphate compound (12). twenty

3. Implant according to claim 2, characterized in that additional outer surfaces (32, 33) of the implant (2), having an oxide layer, are coated with a layer of calcium phosphate compound (12) or with a agent layer (13) that stimulates bone growth.

Implant according to claim 2 or 3, characterized by surfaces that do not have a porous oxidation layer, which are coated with calcium phosphate compound and agent that stimulates bone growth or only with calcium phosphate compound or only agent that stimulates bone growth.

5. Implant according to any of claims 2 to 4, characterized in that the oxide layer (1b) with the The pore arrangement and the calcium phosphate compound layer (12) form a main reservoir for the agent layer (13) that stimulates bone growth. 6. Implant according to any of claims 2 to 5, characterized in that the phosphate compound layer of calcium (12) has a thickness within the range of a few Angströms and 20 µm, and because the layer of agent 35 (13) that stimulates bone growth has a thickness between a few Angströms and 1 µm. 7. Implant according to any of claims 2 to 6, characterized in that the layer of calcium phosphate compound (12) constitutes a substantially amorphous calcium phosphate compound, sputtered cathodically on the surface of the implant, which is then heat treated . 8. Implant according to any of claims 2 to 7, characterized in that the layer of calcium phosphate compound (12) is formed with subsidence that contributes to increase the stability of the agent (13) that stimulates bone growth in the layer of calcium phosphate compound (12). Implant according to any one of claims 2 to 8, characterized in that the layer of calcium phosphate compound (12) has a degree of crystallization of 25 to 75%. 10. Implant according to any of claims 2 to 8, characterized in that the phosphate compound layer Calcium (12) has a degree of crystallization of 75 to 100%. fifty 11. Implant according to any of claims 2 to 8, characterized in that three layers of calcium phosphate compound (12) with different degrees of crystallization are arranged, the first layer having a degree of crystallization of 75% to 100%, having the second layer a degree of crystallization of 25 to 75%, and the third layer being amorphous.